Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation
Authors: Michel Azizi, Felix Mahfoud, Michael A. Weber, Andrew S. P. Sharp, Roland E. Schmieder, Philipp Lurz, Melvin D. Lobo, Naomi D. L. Fisher, Joost Daemen, Michael J. Bloch, Jan Basile, Kintur Sanghvi, Manish Saxena, Philippe Gosse, J. Stephen Jenkins, Terry Levy, Alexandre Persu, Benjamin Kably, Lisa Claude, Helen Reeve-Stoffer, Candace McClure, Ajay J. Kirtane, Christopher Mullin, Lisa Thackeray, Glenn Chertow, Thomas Kahan, Harold Dauerman, Steven Ullery, J. Dawn Abbott, Andreas Loening, Ron Zagoria, John Costello, Courtney Krathan, Luot Lewis, Andrew McElvarr, John Reilly, Michael Cash, Shannon Williams, Maria Jarvis, Pete Fong, Cheryl Laffer, James Gainer, Mark Robbins, Sherron Crook, Sarita Maddel, David Hsi, Scott Martin, Edward Portnay, Maryanne Ducey, Suzanne Rose, Elizabeth DelMastro, Sripal Bangalore, Stephen Williams, Stanley Cabos, Carolina Rodriguez Alvarez, Thomas Todoran, Eric Powers, Emily Hodskins, Vijay Paladugu, Anna Tecklenburg, Chandan Devireddy, Janice Lea, Bryan Wells, Amanda Fiebach, Claudia Merlin, Florian Rader, Suhail Dohad, Hyun-Min Kim, Mohammad Rashid, Josephine Abraham, Theophilus Owan, Anu Abraham,  Iran Lavasani, Hailey Neilson, David Calhoun, Thomas McElderry, William Maddox, Suzanne Oparil, Sheila Kinder, Jai Radhakrishnan, Candido Batres, Suzanne Edwards, Joseph Garasic, Doug Drachman, Randy Zusman, Kenneth Rosenfield, Danny Do, Matheen Khuddus, Suzanne Zentko, James O'Meara, Ilie Barb, Abby Foster, Alice Boyette, Yale Wang, Desmond Jay, Nedaa Skeik, Robert Schwartz, Rose Peterson, Jo Anne Goldman, Jessie Goldman, Gary Ledley, Nancy Katof, Srinivasa Potluri, Scott Biedermann, Jacquelyn Ward, Megan White, Laura Mauri, Piotr Sobieszczky, Alex Smith, Laura Aseltine, Rick Stouffer, Alan Hinderliter, Eric Pauley, Tyrone Wade, David Zidar, Mehdi Shishehbor, Barry Effron, Marco Costa, Terence Semenec, Chanwit Roongsritong, Priscilla Nelson, Bridget Neumann, Debbie Cohen, Jay Giri, Robin Neubauer, Thu Vo, Atul R. Chugh, Pei-Hsiu Huang, Powell Jose, John Flack, Robert Fishman, Michael Jones, Todd Adams, Christopher Bajzer, Anthony Mathur, Ajay Jain, Armida Balawon, Olivier Zongo, Clare Bent, David Beckett, Nicki Lakeman, Sarah Kennard, Richard J. D’Souza, Sarah Statton, Lindsay Wilkes, Christine Anning, Jeremy Sayer, Sudha Ganesh Iyer, Nicholas Robinson, Annaliza Sevillano, Madelaine Ocampo, Robert Gerber, Mohamad Faris, Andrew John Marshall, Janet Sinclair, Hayley Pepper, Justin Davies, Neil Chapman, Paula Burak, Paula Carvelli, Sachin Jadhav, Jane Quinn, Lars Christian Rump, Johannes Stegbauer, Lars Schimmöller, Sebastian Potthoff, Claudia Schmid, Sylvia Roeder, Joachim Weil, Lukas Hafer, Tolga Agdirlioglu, Tanja Köllner, Michael Böhm, Sebastian Ewen, Saarraaken Kulenthiran, Angelika Wachter, Christina Koch, Karl Fengler, Karl-Philipp Rommel, Kai Trautmann, Martin Petzold, Christian Ott, Axel Schmid, Michael Uder, Ulrike Heinritz, Kerstin Fröhlich-Endres, Sabine Genth-Zotz, Denise Kämpfner, Armin Grawe, Johannes Höhne, Bärbel Kaesberger, Constantin von zur Mühlen, Dennis Wolf, Markus Welzel, Gudrun Heinrichs, Barbara Trabitzsch, Antoine Cremer, Hervé Trillaud, Panteleimon Papadopoulos, Florent Maire, Julie Gaudissard, Marc Sapoval, Marine Livrozet, Aurélien Lorthioir, Laurence Amar, Valérie Paquet, Atul Pathak, Benjamin Honton, Marianne Cottin, Frédéric Petit, Pierre Lantelme, Constance Berge, Pierre-Yves Courand, Fatou Langevin, Pascal Delsart, Benjamin Longere, Guillaume Ledieu, François Pontana, Coralie Sommeville, Fabien Bertrand, Lida Feyz, Victor Zeijen, Arno Ruiter, Elisabeth Huysken, Peter Blankestijn, Michiel Voskuil, Zwaantina Rittersma, Helma Dolmans, A.A. Kroon, W.H. van Zwam, Jeannique Vranken, Claudia de Haan., Jean Renkin, Frédéric  Maes, Christophe Beauloye, Jean-Philippe Lengelé, Dominique Huyberechts, Anne Bouvie, Adam Witkowski, Andrzej Januszewicz, Jacek Kądziela, Aleksander Prejbisj, Dagmara Hering, Dariusz Ciecwierz, Milosz J. Jaguszewski, Radoslaw Owczuk
Journal: JAMA Cardiology (2022)

Importance Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. Objectives To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. Design, Setting, and Participants This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m 2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. Interventions uRDN vs sham procedure in conjunction with added medications to target BP control. Main Outcomes and Measures Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. Results A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m 2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of −2.4 [16.6] vs −7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. Conclusions and Relevance In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. Trial Registration ClinicalTrials.gov Identifier: NCT02649426